Institute for Research in Biomedicine
Publishes on Cancer Cells and Metastasis, Management and Organizational Studies, Knowledge Management and Sharing. 24 papers and 2.7k citations.
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This article explores problems caused by nonrespondents in sociometric studies of organizational communication and describes how networks that include nonrespondents can be analyzed. An illustrative example is used to conceptualize the problems and issues in analyzing such networks. An empirical study is described that operationalizes the decision criteria for choosing a method of analysis. Suggestions are offered for the design of communication network studies that may enhance response rates and provide the information needed to justify how incomplete network data sets may be analyzed.
Abstract The analysis of stem cell hierarchies in human cancers has been hampered by the impossibility of identifying or tracking tumor cell populations in an intact environment. To overcome this limitation, we devised a strategy based on editing the genomes of patient‐derived tumor organoids using CRISPR /Cas9 technology to integrate reporter cassettes at desired marker genes. As proof of concept, we engineered human colorectal cancer ( CRC ) organoids that carry EGFP and lineage‐tracing cassettes knocked in the LGR 5 locus. Analysis of LGR 5‐ EGFP + cells isolated from organoid‐derived xenografts demonstrated that these cells express a gene program similar to that of normal intestinal stem cells and that they propagate the disease to recipient mice very efficiently. Lineage‐tracing experiments showed that LGR 5 + CRC cells self‐renew and generate progeny over long time periods that undergo differentiation toward mucosecreting‐ and absorptive‐like phenotypes. These genetic experiments confirm that human CRC s adopt a hierarchical organization reminiscent of that of the normal colonic epithelium. The strategy described herein may have broad applications to study cell heterogeneity in human tumors.